Evolution of ischemia and neovascularization in a murine model of full thickness human wound healing.
Evolution of ischemia and neovascularization in a murine model of full thickness human wound healing.
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DOI：
10.1111/wrr.12847
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Gibson ALF
中科院分区：
文献类型：
--
作者：
Karim AS;Liu A;Lin C;Uselmann AJ;Eliceiri KW;Brown ME;Gibson ALF
由于动物和人类的解剖学和伤口愈合差异，缺乏适当的动物模型限制了伤口愈合研究的翻译。在这里，我们的特点愈合移植，全层人类皮肤在体内模型的伤口愈合。将从重建手术中获得的全层人皮肤移植到NOD. Cg-KitW 41 J Tyr + Prkdcscid Il 2 rgtm 1 Wjl/CnJ小鼠的背侧。移植后1至12周收获异种移植物，并完成存活率、新血管形成和缺氧的组织学分析。异种移植物的目视检查显示从第四周开始表皮干燥和脱落。到第12周，异种移植物似乎愈合，但已损失初始移植物尺寸的63.05 ± 0.24%。早在2周时就有表皮增生的组织学证据，其进展直到第4周，此时新的表皮从伤口边缘出现。表皮再生在第12周完成，尽管表皮出现肥大。移植后6个月，浸润到异种移植物中的免疫小鼠细胞的初始增加正常化至基线。新血管形成，如蛋白质人CD 31和α平滑肌肌动蛋白的阳性染色所证明的，早在异种移植物和小鼠组织之间的界面处移植后2周就存在。在整个异种移植物中，CD 31和α平滑肌肌动蛋白染色在12周内增加，导致组织的活力更大。同样，在存活和非存活组织的界面处存在增加的缺氧诱导因子1-α表达，这表明缺氧驱动的过程导致早期移植物损失。这些发现说明了人皮肤伤口在缺血环境中的愈合，提供了一个时间轴，用于在小鼠模型中移植后使用全厚度人皮肤来研究人皮肤伤口愈合的机制。
Translation of wound healing research is limited by the lack of an appropriate animal model, due to the anatomic and wound healing differences in animals and humans. Here, we characterize healing of grafted, full-thickness human skin in an in vivo model of wound healing. Full-thickness human skin, obtained from reconstructive operations, was grafted onto the dorsal flank of NOD.Cg-KitW41J Tyr + Prkdcscid Il2rgtm1Wjl/ThomJ mice. The xenografts were harvested 1 to 12 weeks after grafting, and histologic analyses were completed for viability, neovascularization, and hypoxia. Visual inspection of the xenograft shows drying and sloughing of the epidermis starting at week four. By week 12, the xenograft appears healed but has lost 63.05 ± 0.24% of the initial graft size. There is histologic evidence of epidermolysis as early as 2 weeks, which progresses until week 4, when new epidermis appears from the wound edges. Epidermal regeneration is complete by week 12, although the epidermis appears hypertrophied. An initial increase of infiltrating immune mouse cells into the xenograft normalizes to baseline 6 months after grafting. Neovascularization, as evidenced by positive staining for the proteins human CD31 and alpha smooth muscle actin, is present as early as 2 weeks after grafting at the interface between the xenograft and the mouse tissue. CD31 and alpha smooth muscle actin staining increased throughout the xenograft over the 12 weeks, leading to greater viability of the tissue. Likewise, there is increased Hypoxia Inducible Factor 1-alpha expression at the interface of viable and nonviable tissue, which suggest a hypoxia-driven process causing early graft loss. These findings illustrate human skin wound healing in an ischemic environment, providing a timeline for use of full thickness human skin after grafting in a murine model to study mechanisms underlying human skin wound healing.
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影响因子：
4.1
作者：
Leibovitch, I;Huilgol, SC;Selva, D
通讯作者：
Selva, D
影响因子：
--
作者：
Richter, Gresham T.;Bowen, Travis;Vural, Emre
通讯作者：
Vural, Emre
DOI：
10.1186/1750-1164-7-1
发表时间：
2013-01-07
期刊：
Annals of surgical innovation and research
影响因子：
--
作者：
Gurtner GC;Jones GE;Neligan PC;Newman MI;Phillips BT;Sacks JM;Zenn MR
通讯作者：
Zenn MR
影响因子：
2.9
作者：
Grishagin, Ivan V.
通讯作者：
Grishagin, Ivan V.
影响因子：
3.6
作者：
Dunkin, Christopher S. J.;Pleat, Jonathon M.;McGrouther, D. Angus
通讯作者：
McGrouther, D. Angus